Enhanced Tubular Dentin Regeneration Via Foxq1-Wnt5a Axis Activation

Regeneration of tubular dentin structure is key to its biological function, and the polarity of odontoblasts is crucial for this, but the mechanism is unclear. We hypothesized that Foxq1, a key regulator in embryo development, contributes to the differentiation of polarized odontoblasts. We tracked Foxq1’s spatiotemporal expression in tooth germs during embryonic stages as well as postnatal stages and studied its effect on tooth development by manipulate Foxq1 level in mesenchyme locally. Dental papilla cells (DPCs) were extracted from E14.5 mouse embryos for in vitro studies and osteogenic, odontogenic and polarization marker expression evaluation. We also investigated the relationship between Foxq1 and Wnt5a. Finally, we validated their actions in vivo. Results showed Foxq1 was expressed in dental mesenchyme and its overexpression promoted dentin thickness and odontoblastic polarization, while suppression reduced tooth germ size and disrupted polarity and dentin formation. WNT5A protein reversed these changes caused by Foxq1 suppression. We proved Foxq1 could bind to the promoter region of Wnt5a and Dspp. In vivo, both Foxq1+DPCs and Wnt5a+DPCs promoted regeneration of de novo tubular-dentin-like structures on inner surface of acellular root canal. We concluded activation of Foxq1-Wnt5a signaling axis promotes polarity and odontogenic differentiation of DPCs, and promote regeneration of tubular dentin structure.